Oseltamivir phosphate, marketed by Roche under the brand name Tamiflu®, is an antiviral medication that is used to treat and prevent influenza A and influenza B (flu). It is recommended for people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. Given the severe flu pandemics in 2009-2010 and in 2017-2018, there is a high demand for the development of even more robust and economical production routes of Tamiflu®.
Many current production routes rely on expensive shikimic acid (current cost is approximately $109/gram) as the starting material. The reported overall yield in one disclosed 12-step synthetic route is about 16.5%. Among these steps, at least four steps involve either cryogenic cooling (−34° C.) or heating (>60° C.). Since the development of Roche's Tamiflu® synthesis, a range of syntheses of Tamiflu® have been developed in academic labs; however, it is not believed that any of them have been commercialized in the US.
There remains a need for oseltamivir production routes that neither involve the usage of expensive starting materials like shikimic acid nor involve tedious synthetic steps, especially those are related the installation of two nitrogen-based groups.